Kazan University Labs Work on Ways to Fight Dangerous Bacteria

Molecular biology is on the forefront of contemporary research in treating the deadliest diseases.

Structural biology – one of the priorities of research work at KFU – emerged about 50 years ago when DNA replication mechanisms were discovered and described. New explorations in cell functioning open new breathtaking horizons in medicine.

Head of the Structural Biology Lab at Kazan University, Professor at Strasbourg University Marat Yusupov spoke in detail about why molecular biology is so important.

- Our work lies in biochemistry and biophysics fields, i. e. studying of biological processes by means of chemical and physical methods.

The goal of our laboratory is to thoroughly study protein synthesis in Staphylococcus cells. This is necessary to understand what weak spots does it have and how to cease its functioning and thus help affected patients.

Currently we use antibiotics to eliminate bacteria inside human body. The problem is there are staph strains that cannot be destroyed by any of the existing medications, and sometimes even properly treated pneumonia ends in death. Unfortunately, there are numerous cases worldwide. But we can avoid this if we study these bacteria.

Out of many cell mechanisms we chose protein synthesis inhibition, namely, its main component – ribosomes. Why that? There is a cell structure that disables ribosome functioning under stress conditions by activating ribosomal dimers. In this form a ribosome does not function and only goes back up after the stressful factor is eliminated.

- Structural biology does not only deal with pathogens but also with regulating processes in human cells?

- Yes, one of the popular topics in structural biology is cancer therapy that requires more and more information about cell mechanisms and their chemical and physical interpretation. With understanding comes an antidote. There is immense progress in this field.

One of the positive examples here is the 90% chance of curing breast cancer nowadays – that is an achievement of molecular biologists, including structural biologists.

Research team of the Structural Biology Lab (Marat Yusupov on the right)

Structural biologists also tackle hereditary ailments.

Our body – hair, nails, muscles – consists of different types of proteins. For the most part in our cells, though, they are enzymes that are responsible for basic organism functions. So, if you turn a ribosome on or off, you can regulate everything that happens in the body. This is a stage of editing genetic information in the DNA. A protein is an amino acid sequence, DNA is a nucleic acid sequence, i. e. the information in DNA and proteins is written down in two different languages. Ribosomes are “translators” of this information. That's why it's so important to learn to regulate their activities.

This is especially pertinent for genetic disease therapy. Genetic diseases are caused by mutations in parents' genes. At some stage the process of transferring from DNA to proteins by ribosomes becomes corrupted. A sequence of genes read by a ribosome begins and ends in specific points, a specific number of nucleotides is read, and then that information transfers into a protein that has some functions in a cell. So if there is a mutation somewhere in the middle of that sequence that disables further “reading”, a ribosome aborts the process, and a protein ends up incomplete as a non-functional piece.

This leads to hereditary syndromes. There are about 300 currently known to us. Scientists try to make ribosomes read all the information even there are such stop mutations. This is also a problem of structural biology.

Fortunately, there are already positive results. A research group from Los Angeles made a ribosome read corrupted DNA during an experiment. There was no satisfactory explanation, so the scientific community did not properly recognize the results, and the project was cancelled. However, the tests were already underway, and after some test patients filed a lawsuit the tests were resumed. After that the company managed to attract 120 million dollars in investment.

There are similar processes around the world. Labs like ours work together with hospitals to create new medications.

- What other pathogens are studied in the world?

- Many of them. In Latin America Trypanosoma – parasitic protozoa - are studied. They are vector-borne pathogens that cause Chagas disease and sleeping sickness.

Another interesting example is Leishmania – it drew much attention after affecting American troops in Iraq.

On methodology

- We use contemporary methods of biophysics and biochemistry, our research group comprises employees of several institutes. There are biologists and physicists, we also plan to add chemists. We utilize nuclear magnetic resonance, microscopy.

Our main limitation is that KFU currently lacks two of the three necessary methods. One of them is cryoelectronic microscopy that allows to study frozen specimens basically on a molecular level. The other is X-ray structural analysis that allows to study protein structure on an atomic level, you can make 3D models and predict which inhibitors and small molecules can deactivate a specific protein.

There are few research centers where all three technologies are available. One of them is Weizmann Institute in Israel – their group is headed by Nobel laureate Ada Yonath.

- I think that Kazan University has done a stunning job in reformatting the biological faculty and creating the environment for collaborating with physicists, chemists, and doctors. This will undoubtedly bring fruit in the future. It's important that the University has its own clinic and a full cycle of research and development. This is a great project that will in its entirety be evaluated by further generations.